The Effect Of BTLA On The Development And Function Of Regulatory T Cellsand The Effect Of BTLA On The Development Of B Cell And BCR Signal

PART ⅠTHE EFFECT OF BTLA ON THE DEVELOPMENT AND FUNCTION OF REGULATORY T CELLSObjective: To explore the direct effects of B and T lymphocyte attenuator(BTLA)on the development and function of regulatory T cells(Treg).Methods: We established the mouse model of selective knockout of BTLA gene in regulatory T cells to study the peripheral environment homeostasis of T cells in the central and peripheral lymphoid organs of mice,the activation of T cells,the production of cytokines,the regulatory T cell development and its function-related molecule expression,and then explore the inhibitory effect of Treg cells in vitro.Result: Comparing with wild type mice,we found that the T cell peripheral environment homeostasis and T cell activation ofthe central and peripheral lymphoid organs of BTLA selectively knocked out mouse,as well as regulatory T cell development,revealed no significant difference.Also,the production of cytokines in BTLA selectively knocked out mouse were comparable with that in wild type mice;the Treg cell inhibitory function test in vitro found that the inhibitory function of regulatory T cells was not significantly different from wild type.Conclusion: BTLA has no direct effect on the development and functional expression of Treg.PART ⅡTHE EFFECT OF BTLA ON THE DEVELOPMENT OF B CELL AND BCR SIGNALObjective:To explore the effect of B and T lymphocyte attenuator(BTLA)on the development and function of B lymphocytes and BCR signal.Methods:A mouse model of specifically knocking out the BTLA gene in B lymphocytes was constructed,detect the peripheral environment homeostasis and functional molecule expression of B cells in the bone marrow,spleen and other lymphoid organs of the model mice,and to study the differential proliferation of B cells after stimulation in vitro,analyze the influence of pY,pBtk recruitment to BCR clusters in B cells stimulated by sAg and the expression of phosphorylation molecules pY,pBTK,pCD19,pPI3 K,pAKT,pS6 after B cell activation.Result:Compared with wildtype mice,B lymphocytes in mice with selective knockout of BTLA in the bone marrow,spleen and peritoneal cavity B cells in peripheral environment homeostasis and functional molecule expression were not found to be significantly different;while the deletion BTLA of B lymphocytes enhanced the proliferation of B lymphocytes stimulated in vitro,and the deletion of BTLA gene enhanced BCR activation and phosphorylation of pY,pBTK,and the phosphorylation of downstream molecules pCD19,pPI3 K,pAKT,and pS6.Conclusion: The expression of BTLA gene has been confirmed to have an inhibitory effect on BCR activation,and it plays an important role in the BCR signal pathway.